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Targeted Superantigens for Immunotherapy of Haematopoietic Tumours
Author(s) -
Tötterman T.H.,
Gidlöf C.,
Ragnarsson L.,
Högbom E.,
Lindeberg M.,
Lehr N.,
Einarsson A.,
Sœgaard M.,
Kristensson K.,
Kalland T.,
Dohlsten M.
Publication year - 1998
Publication title -
vox sanguinis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.68
H-Index - 83
eISSN - 1423-0410
pISSN - 0042-9007
DOI - 10.1111/j.1423-0410.1998.tb05461.x
Subject(s) - immunotherapy , immunology , lymphoma , monoclonal antibody , myeloid , cancer research , haematopoiesis , medicine , superantigen , cytotoxic t cell , chimeric antigen receptor , b cell , t cell , biology , antibody , stem cell , in vitro , immune system , biochemistry , genetics
With the exception of childhood common acute lymphoblastic leukaemia (cALL), treatment of other hematopoietic B cell lineage tumours such as non‐ Hodgkin's lymphoma (B‐NHL), adult ALL and multiple myeloma (MM) is unsatisfactory. Similarly, the therapeutic outcome of acute and chronic myeloid leukaemia (AML, CML) is frequently dismal. At the same time, leukae‐ mia/lymphoma cells represent ideal targets for immunotherapy. The present review summarizes our preclinical experience with a novel type of cytotoxic T cell based immunotherapy for B‐lineage and myeloid tumours. Staphylococcal enterotoxin‐derived superantigens (SAgs) are among the most potent T cell activators known, linking the T cell receptor to HLA‐DR on natural target cells. SAgs were genetically engineered to reduce DR binding and were then fused to Fab parts of tumour‐directed monoclonal antibodies (mAbs). Using these “targeted” SAgs, highly efficient lysis of B‐lineage (B‐NHL, B‐CLL, ALL, MM) and myeloid (AML, CML) tumour cells by T‐cells was achieved in vitro and in an animal model. We are entering an interesting era of innovative cancer therapy based on novel man‐made biotherapeutic agents.